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Warning note on male infertility treatment
had an immediate response to cholestyramine (within 24 h). There was a striking reduction in stool frequency after therapy (median stool frequency pretreatment five per day vs two per day post-treatment, p=0-03, Wilcoxon matched pairs test). Two patients could not tolerate treatment and showed no change in bowel frequency. IBAM is easily diagnosed and frequently simulates postinfectious IBS. Response to treatment is often very good. The mechanism of postinfectious IBAM might be related to a selective impairment of the active bile-acid transport mechanism, and we suggest that IBAM should be considered before any patients are labelled as having postinfectious IBS. L
Sinha, R Liston, T Testa, *K J Moriarty
*Bolton General Hospital, Farnworth, Bolton BL4 Manchester Royal Infirmary, Manchester
OJR, UK; and
1
Gwee KA, Graham JC, McKendrick MW, et al. Psychometric scores and persistence of irritable bowel after infectious diarrhoea. Lancet
2
Sinha L, Liston R, Moriarty KJ. Idiopathic bile acid malabsorption (IBAM) and response to cholestyramine therapy. Gut 1995; 37 (suppl 2): A13. Merrick MV, Eastwood MA, Anderson JR, Ross HM. Enterohepatic circulation in man of a gamma-emitting bile acid conjugate, 23-selena25-homotaurocholic acid (SeCHAT). J Nucl Med 1982; 23: 126—30. Hofmann AF, Poley JR. Cholestyramine treatment of diarrhoea associated with ileal resection. N Engl J Med 1969; 281: 397-402.
1996; 347: 150-53.
3
4
Warning note
on
male
infertility treatment
SIR-Intracytoplasmic sperm injection (ICSI) represents an important approach to the treatment of male factor infertility. The application of this procedure is burgeoning and we think that this progression has been premature: there is an absence of experimental and clinical evidence for the safety of this technique. Although Feichtinger and colleagues (Dec 9, p 1566)’ exclude chromosomal risk in ICSI, In’t Veld and colleagues2 have reported a preponderence of sex chromosome abnormalities in pregnancies after ICSI. Male factor infertility has an unknown cause in a large percentage of cases, and severe oligospermia has been linked to deletions present on the long arm of Y chromosome.3 We have tested this possibility in ten severely oligospermic men before ICSI and we recorded a deletion in the locus Yq 11.23 in three. In these cases the genetic abnormality would of course be
abnormalities and 3
intracytoplasmic
sperm
injection. Lancet 1995; 346:
773. Ma K,
Inglis JD, Sharkey A, et al. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 1993; 75: 1287-95.
Vascular sounds in
hypertensive pregnancy
SiR-Shennan and colleagues (Jan 20, p 139),’ from studies of non-pregnant and normotensive pregnant women, propose new international recommendations regarding the diagnosis and management of hypertensive disorders in pregnancy. The basis for existing recommendations to use phases I and IV of the vascular sounds is that they provide pragmatic thresholds for the diagnosis of mild (140/90, phase I/IV) and severe (160/100, phase I/IV) hypertension in pregnancy.2 Phase IV corresponds to the return of continuous flow through the brachial artery, and usually occurs one or two waveforms before phase V in normotensive individuals (figure, top, from Quinn3). Vascular sound audible to zero have only been objectively observed in parous women with very compliant circulations, and these sounds do not present a substantial reason for the adoption of phase IV over phase V (figure, lower3). Are existing criteria effective in reducing maternal morbidity from hypertensive disease? The British Eclampsia Survey Team noted that 294 of 383 cases of confirmed eclampsia occurred in hospital, 227 of 383 had typical symptoms of impending eclampsia, although only 69 of 294 had measured raised blood pressures (>120 mm Hg).4 Either there has been a striking increase in the incidence of normotensive eclampsia (that seems unlikely), or else, underestimation of blood pressure in patients with reduced circulatory compliance is common. Substantial underrecording of phase I and phase IV (up to 30 mm Hg) by automated devices in severe proteinuric hypertensive individuals has been recorded, and these devices are in widespread use despite not being validated in severe hypertension.*’ Shennan and colleagues’ suggestion that
in-situ fluorescence the hybridisation (FISH), presence of sex investigated chromosome abnormalities in ejaculated sperm from ten other men with severe oligospermia, finding sex chromosome diploidy in 15-20% of the examined sperm in three men. These alterations are present also in sperm from normospermic men, although in a very low percentage. However, fertilisation in vivo requires a fully competent spermatozoon, and most sperm do not, of course, participate in the fertilisation process. ICSI bypasses this selection, thereby increasing the risk of fertilisation by abnormal transmitted.
Furthermore,
with
we
sperm. We suggest caution in the
of sperm for ICSI in the of severe idiopathic presence oligospermia, and we recommend thorough clinical investigation of infertile men, and sperm before ICSI. use
*Carlo Foresta, Alberto Ferlin, Carlo Galeazzi, Marco Rossato of Padova, Patologia Medica III, 35128 Padova, Italy
University
1
2
Feichtinger W, Obruca A, Brunner M. Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet 1995; 346: 1566. In’t Veld P,
618
Brandenburg H, Verhoeff A,
et
al. Sex chromosomal
Figure: Relation of changes in brachial artery waveform (75 MHz doppler, Toshiba SSA-270) to vascular sounds (phase I-V) in a normotensive, nulliparous woman in third trimester of pregnancy (upper), and absence of phase V of vascular sounds in a normotensive multiparous woman in third trimester of pregnancy (lower) Upper: phase I is associated with onset of flow in vessel, phase II is associated with reactive hyperaemia, phase III is associated with onset of reverse flow, phase IV is associated with continuous flow, phase V is not associated with large alterations in brachial artery waveform. Lower: similar sequence is observed to normotensive nulliparous woman, though the vascular sounds are audible with a stethoscope at rest. (Reproduced from reference 3, with permission, from Ultrasound in Obstetrics & Gynecology, Parthenon Publishing Group.)
Sinha, R Liston, T Testa, *K J Moriarty
*Bolton General Hospital, Farnworth, Bolton BL4 Manchester Royal Infirmary, Manchester
OJR, UK; and
1
Gwee KA, Graham JC, McKendrick MW, et al. Psychometric scores and persistence of irritable bowel after infectious diarrhoea. Lancet
2
Sinha L, Liston R, Moriarty KJ. Idiopathic bile acid malabsorption (IBAM) and response to cholestyramine therapy. Gut 1995; 37 (suppl 2): A13. Merrick MV, Eastwood MA, Anderson JR, Ross HM. Enterohepatic circulation in man of a gamma-emitting bile acid conjugate, 23-selena25-homotaurocholic acid (SeCHAT). J Nucl Med 1982; 23: 126—30. Hofmann AF, Poley JR. Cholestyramine treatment of diarrhoea associated with ileal resection. N Engl J Med 1969; 281: 397-402.
1996; 347: 150-53.
3
4
Warning note
on
male
infertility treatment
SIR-Intracytoplasmic sperm injection (ICSI) represents an important approach to the treatment of male factor infertility. The application of this procedure is burgeoning and we think that this progression has been premature: there is an absence of experimental and clinical evidence for the safety of this technique. Although Feichtinger and colleagues (Dec 9, p 1566)’ exclude chromosomal risk in ICSI, In’t Veld and colleagues2 have reported a preponderence of sex chromosome abnormalities in pregnancies after ICSI. Male factor infertility has an unknown cause in a large percentage of cases, and severe oligospermia has been linked to deletions present on the long arm of Y chromosome.3 We have tested this possibility in ten severely oligospermic men before ICSI and we recorded a deletion in the locus Yq 11.23 in three. In these cases the genetic abnormality would of course be
abnormalities and 3
intracytoplasmic
sperm
injection. Lancet 1995; 346:
773. Ma K,
Inglis JD, Sharkey A, et al. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 1993; 75: 1287-95.
Vascular sounds in
hypertensive pregnancy
SiR-Shennan and colleagues (Jan 20, p 139),’ from studies of non-pregnant and normotensive pregnant women, propose new international recommendations regarding the diagnosis and management of hypertensive disorders in pregnancy. The basis for existing recommendations to use phases I and IV of the vascular sounds is that they provide pragmatic thresholds for the diagnosis of mild (140/90, phase I/IV) and severe (160/100, phase I/IV) hypertension in pregnancy.2 Phase IV corresponds to the return of continuous flow through the brachial artery, and usually occurs one or two waveforms before phase V in normotensive individuals (figure, top, from Quinn3). Vascular sound audible to zero have only been objectively observed in parous women with very compliant circulations, and these sounds do not present a substantial reason for the adoption of phase IV over phase V (figure, lower3). Are existing criteria effective in reducing maternal morbidity from hypertensive disease? The British Eclampsia Survey Team noted that 294 of 383 cases of confirmed eclampsia occurred in hospital, 227 of 383 had typical symptoms of impending eclampsia, although only 69 of 294 had measured raised blood pressures (>120 mm Hg).4 Either there has been a striking increase in the incidence of normotensive eclampsia (that seems unlikely), or else, underestimation of blood pressure in patients with reduced circulatory compliance is common. Substantial underrecording of phase I and phase IV (up to 30 mm Hg) by automated devices in severe proteinuric hypertensive individuals has been recorded, and these devices are in widespread use despite not being validated in severe hypertension.*’ Shennan and colleagues’ suggestion that
in-situ fluorescence the hybridisation (FISH), presence of sex investigated chromosome abnormalities in ejaculated sperm from ten other men with severe oligospermia, finding sex chromosome diploidy in 15-20% of the examined sperm in three men. These alterations are present also in sperm from normospermic men, although in a very low percentage. However, fertilisation in vivo requires a fully competent spermatozoon, and most sperm do not, of course, participate in the fertilisation process. ICSI bypasses this selection, thereby increasing the risk of fertilisation by abnormal transmitted.
Furthermore,
with
we
sperm. We suggest caution in the
of sperm for ICSI in the of severe idiopathic presence oligospermia, and we recommend thorough clinical investigation of infertile men, and sperm before ICSI. use
*Carlo Foresta, Alberto Ferlin, Carlo Galeazzi, Marco Rossato of Padova, Patologia Medica III, 35128 Padova, Italy
University
1
2
Feichtinger W, Obruca A, Brunner M. Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet 1995; 346: 1566. In’t Veld P,
618
Brandenburg H, Verhoeff A,
et
al. Sex chromosomal
Figure: Relation of changes in brachial artery waveform (75 MHz doppler, Toshiba SSA-270) to vascular sounds (phase I-V) in a normotensive, nulliparous woman in third trimester of pregnancy (upper), and absence of phase V of vascular sounds in a normotensive multiparous woman in third trimester of pregnancy (lower) Upper: phase I is associated with onset of flow in vessel, phase II is associated with reactive hyperaemia, phase III is associated with onset of reverse flow, phase IV is associated with continuous flow, phase V is not associated with large alterations in brachial artery waveform. Lower: similar sequence is observed to normotensive nulliparous woman, though the vascular sounds are audible with a stethoscope at rest. (Reproduced from reference 3, with permission, from Ultrasound in Obstetrics & Gynecology, Parthenon Publishing Group.)